1. Field of the Invention
This invention relates to biological activity, and more particularly, it relates to medical devices having improved antimicrobial surfaces and to a method to inhibit microorganism growth in a living body during their use.
2. Description of the Prior Art
Infection is a frequent complication of indwelling medical devices such as vascular, and, in particular, urinary catheters. A high percentage of patients who require long-term urinary catheters develop chronic urinary tract infections, frequently in conjunction with episodes of fever, chills, and flank pain. Such patients are at risk of developing bacteremia or chronic pyelonephritis, conditions of high morbidity and mortality.
The magnitude of the urinary tract infection (UTI) problem is clearly indicated by statistics showing that 10-15% of hospital patients need urinary catheters and about 25% of those develop infection. Put another way, UTI accounts for 40% of all nosocomial infections and involves an estimated 800,000 patients a year.
Many studies have demonstrated that bacterial contamination of the urinary drainage bag during catheterization is a frequent source of bladder bacteriuria, and that addition of various antibacterial and antifungal agents, such as hydrogen peroxide, reduce or delay the incidence of bacteriuria. Coatings of antibacterial agents on catheters have likewise been known to delay development of bacteriuria. Thompson et al. (J. Am. Med. Assoc. 251 747-51 (1984)), however, showed that infections arising intraluminally from drainage bag contamination are uncommon among catheterized patients and that periodic instillation of disinfectants into closed, sterile drainage systems is not effective in reducing the incidence of catheter-associated bacteriuria. Their data suggest that extraluminal migration in the periurethral mucous sheath is the major route of bacterial entry into the catheterized urinary tract.
Another important part of medical care is infusion of drugs and fluid with intravenous catheters. Contamination of the infusion system is common and may result in septicemia. It has been suggested that microorganisms may gain access to the tip of a cannula both at the moment of insertion and subsequently by migration along the interface between the catheter and tissue.
U.S. Pat. No. 4,253,463 to Kim teaches a method of reducing infection during use of an intravascular device. The method includes applying to the device a coating of a common metal, such as aluminum or tin, which contacts the tissue of the patient at the point of entry of the device.
Silver compounds have long been used in clinical medicine because of their antiseptic properties. Two examples of such use of silver compounds are the prophylaxis of ocular infections and prevention and treatment of burn-wound sepsis. Beginning in the late 19th century, metallic silver in the form of sutures and foils was used to produce bacteriostatic effects via the passive dissociation of silver from the metallic phase into tissue. A review of this work with silver alone or in combination with other metals is given by Romans, "Oligodynamic Metals" (Chapter 24) and "Silver Compounds" (Chapter 28), Disinfection, Sterilization and Preservation, C. A. Lawrence and S. S. Bloek, ed., Lea and Fibiger, 1968.
Inhibition of the growth of bacteria and fungi by ions of stainless steel, silver, gold and platinum generated at electrodes had been reported by Spadaro et al. (Antimicrobial Agents and Chemotherapy 6, 637 (1974).
Marino et al. (J. Electrochem. Soc. 132, 68 (1985)) disclose wound dressings consisting of fabrics which are rendered antiseptic by coating with metallic silver and application of externally generated current through tabs serving as electrodes.
U.S. Pat. No. 4,054,139 to Crossley teaches reduction of catheter-associated infection by oligodynamic amounts of silver, or silver mixed with another heavy metal, such as gold, on both the interior and exterior surfaces of the catheter.
Akiyama et al. (J. Urology 121, 40 (1979)) discloses a modified urinary catheter and drainage system which includes a Foley catheter coated with silver powder and a silver plated connector between the flared end of the catheter and the synthetic drainage tube. The system utilizes the bacteriostatic property of silver ions to reduce urinary tract infection due to prolonged bladder catheterization. In U.S. Pat. No. 4,483,688 and British Pat. No. 1,582,016, Akiyama discloses use of an oligodynamically active heavy metal, such as copper, silver or gold or alloys thereof to achieve a bacteriostatic effect on the outside surface only of a catheter or urinary drainage system.
Travenol Laboratories, Inc., Medical Products Division, Deerfield, Ill., presently markets a silver coated catheter adapter designed to kill bacteria at the catheter-tubing junction.
Davis et al. in (J. Clin. Microbiology 15, 891 (1982)) describe iontophoretic killing of several bacterial genera by various metals. Only gold iontophoresis killed all bacterial genera. Other metals, such as silver and copper were described as being ineffective. In U.S. Pat. No. 4,411,648, Davis et al. teach a urinary catheter having heavy metal-containing electrodes. Bacterial infection associated with catheterization is iontophoretically prevented by use of externally generated electromotive force. Gold electrodes provide the most effective bactericidal effect. Silver, platinum, copper or stainless steel are less effective at currents which have no significant effect on surrounding tissue.